The proposed research will investigate the relationships between mechanical stimuli and estrogen in maintaining skeletal mass and strength. The study will use ovariectomized female dogs as the experimental model. Fifty dogs will be divided into 5 groups of 10 dogs each: sham operated, exercised; sham operated, delayed exercise; overiectomized, exercised; ovariectomized, delayed exercise; ovariectomized, delayed impulsive loading of the right hind leg by machine. The post-operative observation time will be 15 months. Delayed exercise will begin 9 months post-op; half of the dogs within each group will be sacrificed at the end of the 9 month period to have correlated data in dogs without exercise intervention or mechanical loading. A Bone Mineral Analyzer and x-ray densitometry will be used to monitor skeletal changes during the entire 15 month post-operative period. Serum estrogen levels will be monitored monthly. Treadmill stress testing will be used to quantify exercise activity levels. Changes in muscle size will be measured, and in vivo strain gaging will document bone strains during exercise and machine loading. The strength, composition, and histology of bone from the spine, femurs, tibias, and humeri will be studied post-mortem, and both in vivo and in vitro data will be analyzed to determine if mechanical stimuli may prevent or lead to replacement of bone loss due to estrogen deficiency. The research will clarify the relationship between mechanical and biochemical skeletal controls and the feasibility of using exercise to treat or prevent postmenopausal osteoporosis.